It has been found that administering inhibitors (effectors) of DP IV or DP IV-analogous enzyme activity in the blood of a mammal causes, because of the associated temporary reduction in enzyme activity, reduced breakdown of the endogenous (and also exogenously administered) insulinotropic peptides Gastric Inhibitory Polypeptides 1–42 (GIP1-42) and Glucagon-Like Peptide Amides-1 7–136 (GLP-17-36) (or also GLP-17-37 or analogues thereof) by DP IV and DP IV-like enzymes and, accordingly, the fall in concentration of those peptide hormones, or analogues thereof, is reduced or delayed. The greater stability of (endogenously present or exogenously introduced) incretins or analogues thereof, which results from the action of DP IV-effectors, increases their availability for insulinotropic stimulation of the incretin receptors of the Langerhans cells in the pancreas and alters, inter alia, the effectiveness of the body's own insulin, resulting in stimulation of carbohydrate metabolism in the treated organism. As a result, in the serum of the treated organism, the blood sugar level drops below the glucose concentration that is characteristic of hyperglycaemia. Consequently, by means of DP IV-inhibitors it is possible to prevent or to mitigate metabolic anomalies such as excess weight, glucosuria, hyperlipidaemia and also possible serious metabolic acidoses and diabetes mellitus, which are a consequence of prolonged elevated glucose concentrations in the blood [see DE 196 16 486].
With the aid of DP IV-inhibitors, it is also possible, experimentally, to prevent the penetration of CD 26 (DP IV) positive cells by HIV [see WAKSELMAN, M., NGUYEN, C., MAZELEYRAT, J.-P., CALLEBAUT, C., KRUST, B., HOVANESSIAN, A. G., Inhibition of HIV-1 infection of CD 26+ but not CD 26−cells by a potent cyclopeptidic inhibitor of the DPP IV activity of CD 26. Abstract P 44 of the 24th European Peptide Symposium 1996].
It has also been found that DP IV can modulate the activity of neuroactive peptides, such as neuropeptide Y and CLIP [see MENTLEIN, R., DAHMS, P., GRANDT, D., KRUGER, R., Proteolytic processing of neuropeptide Y and peptide YY by dipeptidyl peptidase IV. Regul. Pept. 49, 133 (1993); WETZEL, W., WAGNER, T., VOGEL, D., DEMUTH, H.-U, BALSCHUN, D., Effects of the CLIP fragment ACTH 20–24 on the duration of REM sleep episodes. Neuropeptides, 31, 41 (1997)].
The problem of the present invention is to provide effectors of DP IV which have an increased action compared with known inhibitors and which have a temporally defined onset of action.